TCR complex-activated CD8 adhesion function by human T cells.
The CD8 receptor plays a central role in the recognition and elimination of virally infected and malignant cells by cytolytic CD8(+) T cells. In conjunction with the TCR, the CD8 coreceptor binds Ag-specific class I MHC (MHC-I) molecules expressed by target cells, initiating signaling events that result in T cell activation. Whether CD8 can further function as an adhesion molecule for non-Ag MHC-I is currently unclear in humans. In this study, we show that in human CD8(+) T cells, TCR complex signaling activates CD8 adhesion molecule function, resulting in a CD8 interaction with MHC-I that is sufficient to maintain firm T cell adhesion under shear conditions. Secondly, we found that while CD8 adhesive function was triggered by TCR complex activation in differentiated cells, including in vitro generated CTL and ex vivo effector/memory phenotype CD8(+) T cells, naive CD8(+) T cells were incapable of activated CD8 adhesion. Lastly, we examine the kinetics of, and signaling for, activated CD8 adhesion in humans and identify notable differences from the equivalent CD8 function in mouse. Activated CD8 adhesion induced by TCR signaling may contribute to the more rapid and robust elimination of pathogen-infected cells by differentiated CD8(+) T cells.
Varghese
Jay C
JC
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Kane
Kevin P
KP
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D017252:CD3 Complex; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D017260:Receptor-CD3 Complex, Antigen, T-Cell